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Biomedical subjects

C M Martelli

Publications and source records attributed to C M Martelli.

At least 19 recordsLinked to original sources

An epidemiological approach to study congenital Chagas' disease.

Transplacental transmission of Trypanosoma cruzi has been the focus of much attention in highly endemic areas in South America. Frequency of congenital transmission and factors associated with risk of it are still not well understood. Parasite strains may account for part of the geographical variation observed. Methodological differences between the studies do not permit a combined interpretation of results. This paper examines the epidemiological data available from Brazil, Bolivia, and Argentina and discusses possible epidemiological study design to investigate risk factors for transmission.

Journal Article↗

Haemophilus influenzae resistance in Latin America: systematic review of surveillance data.

Haemophilus influenzae is a relevant cause of morbidity and mortality among children under 5 years of age in the developing world. In Latin America, H. influenzae type b (Hib) conjugate vaccine and surveillance of H. influenzae antimicrobial susceptibility have been implemented in recent years. We have undertaken a systematic review and a pooled analysis on H. influenzae antimicrobial resistance, including reports of 15 Latin America countries over a 10-year period (1990-2000). We have found that 450 (21.4%) of 2,100 invasive isolates were beta-lactamase producers compared to 145 (14.5%) of 998 isolates of noninvasive isolates (p < 0.05). Ampicillin resistance was detected among 783 (21.9%) of 3,577 invasive isolates compared to 111 (17.2%) of 646 noninvasive strains (p < 0.05). In contrast, 568 (41.9%) of 1,355 noninvasive strains were trimethoprim-sulfamethoxazole (TMP-SMX) resistance against 241 (26.9%) of 897 invasive ones (p < 0.05). Therefore, TMP-SMX resistance was more common in nonsterile fluids than in sterile fluids. Over time, rates of beta-lactamase-producing strains were stable in Brazil and Mexico, whereas rates of TMP-SMX resistance were increasing in Brazil. It is predictable that following the Hib immunization, Latin America countries will be faced with increased nontypeable H. influenzae infection. Although standing by the nontypeable H. influenzae vaccine, in this novel epidemiological scenario of post-Hib vaccination in Latin America settings there is a need to improve H. influenzae resistance monitoring to guide clinicians to choose efficacious antimicrobial therapy.

Data Interpretation, Statistical↗

Distinct histopathological patterns in single lesion leprosy patients treated with single dose therapy (ROM) in the Brazilian Multicentric Study.

This paper aims to describe the histomorphologic features of skin biopsies of single lesion leprosy patients recruited at outpatient clinics in four Brazilian states in the Northeast (Amazonas and Rondonia), Southeast (Rio de Janeiro) and Center-West (Goiás) between October 1997 and December 1998. Patients clinically diagnosed as single skin lesion paucibacillary (SSL-PB) leprosy had a standard 4-mm punch biopsy taken from the lesion before rifampin, ofloxacin, minocycline (ROM) therapy. The features of the cellular inflammatory infiltrates, the presence of nerve involvement and acid-fast bacilli (AFB) were used to categorize SSL-PB biopsies into different histopathological groups. Two-hundred-seventy-eight (93.0%) out of 299 patients had a skin biopsy available. Seven single lesion patients were diagnosed as BL or LL leprosy types (MB) by the histopathological exams and 12 cases were excluded due to other skin diseases. Therefore, 259 patients had skin lesions with histomorphological features compatible with PB leprosy categorized as follows: 33.6% (N = 87) of the biopsies represented well-circumscribed epithelioid cell granuloma (Group 1); 21.6% (N = 56) less-circumscribed epithelioid cell granuloma (Group 2); 12.0% (N = 31) were described as mononuclear inflammatory infiltrate permeated with epithelioid cells (Group 3), and 29.7% (N = 77) had perivascular/periadnexal mononuclear inflammatory infiltrate (Group 4). Minimal/no morphological alteration in the skin was detected in only 8 (3.1%) SSL-PB patients categorized as Group 5, who were considered to have leprosy by clinical parameters. SSL-PB leprosy patients recruited in a multicentric study presented histomorphology readings comprising the whole PB leprosy spectrum but also a few MB cases. These results indicate heterogeneity among SSL-PB patients, with a predominance of well-circumscribed and less-circumscribed epithelioid cell granulomas (Groups 1 and 2) in the sites studied and the heterogeneity of local cellular immune response.

Adult↗

The use of socioeconomic factors in mapping tuberculosis risk areas in a city of northeastern Brazil.

In Brazil the challenge of meeting the needs of those living in deprived areas has generated discussions on replacing the existing approach to epidemiological surveillance with an integrated public health surveillance system. This new approach would supplant the traditional focus on high-risk individuals with a method for identifying high-risk populations and the areas where these persons live. Given the magnitude of the problem that tuberculosis (TB) poses for Brazil, we chose that disease as an example of how such a new, integrated public health surveillance system could be constructed. We integrated data from several sources with geographic information to create an indicator of tuberculosis risk for Olinda, a city in the Brazilian state of Pernambuco. In order to stratify the urban space in Olinda and to check for an association between the resulting TB risk gradient and the mean incidence of the disease between 1991 and 1996, we applied two different methods: 1) a "social deprivation index" and 2) principal component analysis followed by cluster analysis. Our results showed an association between social deprivation and the occurrence of TB. The results also highlighted priority groups and areas requiring intervention. We recommend follow-up that would include treating acid-fast bacilli smear-positive pulmonary TB cases, tracing of these persons' contacts, and monitoring of multidrug-resistant cases, all in coordination with local health services.

Brazil↗

Single lesion paucibacillary leprosy: baseline profile of the Brazilian Multicenter Cohort Study.

In Brazil, there is little information about the clinical and epidemiological characteristics of paucibacillary, single skin lesion leprosy patients (SSL-PB). Only recently has the official notification system distinguished leprosy patients with a single lesion as a clinical entity, for whom the single-dose ROM (rifampin, ofloxacin and minocycline) regimen has been recommended. In this paper, we describe the baseline clinical features and the immunological background of a multicenter cohort of SSL-PB leprosy cases enrolled between December 1997-1998. Patients were recruited at health centers located in the following regions: Southeast = Rio de Janeiro; North = Amazon and Rondônia states and Center-West = Goiás state. Eligible cases were newly detected, untreated single-lesion leprosy patients without thickened nerve involvement, and were assessed by clinical, bacilloscopic and histopathological exams. The Mitsuda skin test and anti-PGL-I serology (ELISA) were also performed. Of the 299 SSL-PB leprosy patients, 259 (86.6%) fulfilled the criteria for single-dose ROM intervention. Our results showed that patients recruited from different sites had similar features, considering the clinical and immunological profiles. There was a predominance of adults (mean age 32.4; S.D. = 16.0), and a BCG scar was detected in 76.7% of the children (< or = 15 years old). Only 7 cases were diagnosed as the multibacillary type, representing less than 3% of the patients being misclassified. Our data indicate that in Brazil SSL-PB case ascertainment based on clinical and bacilloscopic criteria can be accurately defined under a routine control program; 75.0% of SSL-PB cases were Mitsuda positive (> or = 5 mm) and seropositivity for anti-PGL-I was detected in 17.3% of the patients. These data are compatible with effective cell-mediated immunity and low bacillary load, suggesting favorable clinical outcomes for most SSL-PB participants of this cohort.

Adolescent↗

Early electrocardiographic abnormalities in Trypanosoma cruzi-seropositive children.

As part of a major epidemiologic study on Chagas' disease, we compared the prevalence of electrocardiographic (ECG) abnormalities among 141 school children 7-12 years of age and seropositive for Trypanosoma cruzi, and 282 age-, sex-, and school-matched seronegative children in an endemic area in Brazil. The prevalence of ECG abnormalities was 11.3% among seropositive children and 3.5% among seronegative children (odds ratio = 3.5, 95% confidence interval [CI] = 1.5-8.4). The prevalence rate of ECG alterations was 10.7% for seropositive males versus 8.9% for seropositive females. Complete right bundle branch block (CRBBB), which is highly suggestive of Chagas' disease cardiopathy, was diagnosed in nine (6.4%) seropositive children and in only one (0.3%) seronegative child (odds ratio = 18.5, 95% CI = 2.3-146.5, attributable fraction = 58.3%). Five incident new cases of CRBBB were diagnosed after a 36-month follow-up of seropositive children who were enrolled in an independent clinical field trial. No case of frequent and/or multifocal ventricular premature beats was found in the cohort of children. The surprisingly high frequency of early ECG abnormalities, which indicates a rapid evolution from infection to disease, suggests the existence of endemic areas with a particular accelerated disease progression that was not described before. Under such conditions, a public health chemotherapy program focusing on the treatment of young seropositive children would be recommended.

Chagas Disease↗

Assessment of anti-PGL-I as a prognostic marker of leprosy reaction.

The anti-phenolic glycolipid-I (PGL-I) assay as currently applied for leprosy is conceived as an early marker of asymptomatic infection, early disease diagnosis and cure monitoring. Its use as a prognostic marker of reaction is still a matter of controversy. We conducted a case-control study to investigate whether IgM and IgG anti-PGL-I antibodies could discriminate patients at increased risk of developing reactions. Eligible cases were untreated leprosy patients at the onset of type 1 and type 2 reactions recruited from among 600 concurrent, newly detected, untreated leprosy patients attending an outpatient clinic in central Brazil. For the patients with reaction, approximately the same number of leprosy cases without reaction matched as to bacterial index (BI), age and gender were randomly selected. Individuals without clinical leprosy were evaluated as healthy controls. Sera from type 1 reaction (N = 43) and type 2 reaction (N = 26) patients were tested by an ELISA using PGL-I synthetic disaccharide-BSA antigen and 1:300 sera dilution (cut-off point > or = 0.2 OD). Antibody profiles were evaluated by exploratory data analysis and reverse cumulative distribution curves. The IgG anti-PGL-I response did not have a defined pattern, being detected only at low levels. Our results indicate that leprosy patients, independently of their reactional status, produce high levels of IgM anti-PGL-I, demonstrating a strong correlation between the magnitude of antibody response and the BI. Patients with a higher BI were at least 3.4 times more prone to produce an antibody response compared to healthy controls.

Adult↗

Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection.

BACKGROUND: Benznidazole, a nitroimidazole derivative, has been recommended for the treatment of acute and congenital Trypanosoma cruzi infection (Chagas' disease). We have examined the safety and efficacy of this drug in the treatment of the early chronic phase of T cruzi infection. METHODS: Between 1991 and 1995, we carried out a randomised, double-blind, placebo-controlled trial in a rural area of Brazil with endemic Chagas' disease. 82% of 2434 schoolchildren (aged 7-12 years) identified in a census were screened for antibodies to T cruzi by indirect immunofluorescence, indirect haemagglutination, and ELISA. 130 were positive in all tests and were randomly assigned benznidazole (7.5 mg/kg daily for 60 days by mouth) or placebo. The primary endpoint for efficacy was the disappearance of specific antibodies (negative seroconversion) by the end of 3-year follow-up. The secondary endpoint was the reduction of antibody titres on repeated serological tests. One child moved away from the area just after randomisation and was excluded from the analyses. Insecticidal measures were taken throughout the trial to reduce the risk of reinfection. FINDINGS: Minor side-effects requiring no specific medication were recorded in a small proportion of individuals. On a chemiluminescent ELISA with purified trypomastigote glycoconjugate, serum from all participants was positive at the beginning of the trial. At the end of follow-up, 37 (58%) of the 64 benznidazole-treated participants and 3 (5%) of those who received placebo were negative for T cruzi antibodies. The efficacy of benznidazole treatment estimated by intention to treat was 55.8% (95% CI 40.8-67.0). At the end of follow-up, children who received benznidazole had five-fold lower geometric mean titres by indirect immunofluorescence than placebo-treated children (196[147-256] vs 1068[809-1408], p < 0.00001). INTERPRETATION: The trial showed that a 60-day course of benznidazole treatment of early chronic T cruzi infection was safe and 55.8% effective in producing negative seroconversion of specific antibodies. The results are very encouraging and justify the recommendation of treatment for seropositive children as public health policy.

Animals↗

Risk factors for Trypanosoma cruzi infection among children in central Brazil: a case-control study in vector control settings.

This population-based case-control study was conducted in northern Goias State, central Brazil, in rural settings under vector control surveillance. One hundred forty-nine children seropositive for Trypanosoma cruzi antibodies, selected in a cross-sectional survey carried out in village schools, were compared with 298 seronegative classmate controls matched for age, sex, and place of residence. Information on potential environmental, familiar, and social economic risk factors for T. cruzi infection was collected during household visits, and interviews with parents and entomologic inspections of domestic and peridomestic environments were conducted. The presence of triatomines in dwellings or evidence of triatomine colonization was found to be statistically associated with seropositivity in children. The presence of exuviae and a report of triatomines indoors or outdoors by householders in the past were strong predictors of an infected child. Children from seropositive mothers had a 3.9-fold increase in the risk of having anti-T. cruzi antibodies after adjusting for the confounding variables, including triatomine capture, mother's age, and family size in multivariate analysis. Parent's report of vector presence showed a 97.7% sensitivity in identifying a dwelling with at least one seropositive child. The possibility of transplacental T. cruzi transmission and its implication for Chagas' disease control were considered.

Adult↗

Evaluation of risk factors for house infestation by Triatoma infestans in Brazil.

An active entomologic survey was conducted by a team of trained health workers in a rural area endemic for Chagas' disease in central Brazil. They used pyrethrum as a flushing agent and 4,232 houses were inspected for triatomine bugs both inside and in the immediate environs. Houses with Triatoma infestans or evidence of an established colony were identified and defined as infested houses (cases). The building and environmental characteristics of 161 randomly selected infested houses were compared with 161 matched, noninfested houses (controls) that were the shortest distance from the infested house. Domestic and peridomestic potential risk factors associated with house infestation by Triatoma infestans were assessed by logistic regression analysis. Incomplete house construction (odds ratio [OR] = 2.5, 95% confidence interval [CI] = 1.5-4.1) was confirmed as a risk factor related to the presence or evidence of Triatoma infestans in the dwellings. The study also disclosed a statistically significant association between the presence of rats (OR = 1.6, 95% CI = 1.1-2.6) and indoor crop storage (OR = 2.3, 95% CI = 1.1-5.2) and house infestation. Further experimental field studies using tagged rodents should be conducted to assess their epidemiologic role in the domestic chain of Trypanosoma cruzi transmission.

Analysis of Variance↗

Spatial patterns of leprosy in an urban area of central Brazil.

Reported is the spatial variation of leprosy in an urban area of Brazil and its correlation with socioeconomic indicators. From November 1991 to October 1992 a total of 752 newly diagnosed leprosy patients who were attending all outpatient clinics in Goiânia city, central Brazil, were identified. A database o leprosy cases was set up linking patients' addresses to 64 urban districts. Leprosy cases were detected in 86% of the districts and three risk strata were identified. The highest-risk area for leprosy was in the outskirts of the city and detection rates increased on moving from more developed to poorer areas. The risk of detecting leprosy cases was 5.3-fold greater (95% CI: 3.8-7.4) in the outskirts of the town than in the central zone. Discussed are the methodological issues related to leprosy case ascertainment, completeness and reliability of information, and the interpretation of the spatial distribution of leprosy per unit area. Highlighted also are the lack of leprosy control activities in primary health care units and the usefulness of geographical analysis in planning health services.

Adolescent↗

Prevalence and risk factors for HBV infection among street youth in central Brazil.

PURPOSE: A seroprevalence survey was carried out among 496 street adolescents from 9 to 20 years old in central Brazil to determine the prevalence of hepatitis B (HBV) markers, as well as to assess the role of potential risk factors. RESULTS: The findings reveal that 20.4% of the participants were homeless adolescents without family links, living and/or working on the streets. The age at first sexual intercourse was as low as 9 years old, and approximately 60% of this population had had at least one sexual relationship by the age of thirteen, indicating prepubertal initiation of sexual experiences among street adolescents. 13.5% were HBV marker-positive (anti-HBc) and 2.0% had antigenemia. Street-based youth had a higher HBV marker-positive rate when compared to home-based teens (OR = 4.1, 95% CI: 2.1-8.5) and, similarly, higher HBV prevalence was obtained for those reporting sexual activity versus the group without sexual activity (OR = 2.1, 95% CI: 1.1-3.9), even after adjusting for potential confounders. CONCLUSIONS: We have found that street youth, particularly street-based adolescents, should be considered at-risk group for hepatitis B infection in our region. These findings may be used as a baseline information for policy changes not only in hepatitis B prevention but also to reverse the scenario of adolescents sexual abuse.

Adolescent↗

Agreement between histopathological results in clinically diagnosed cases of indeterminate leprosy in São Paulo, Brazil.

Histopathological slides from skin biopsies of fifty-seven self-reporting patients diagnosed as indeterminate leprosy by the Leprosy Control Programme in São Paulo, were sent to three independent histopathologists. Agreement between the reports were based on the following diagnosis: "indeterminate leprosy", "suggestive leprosy" or "no leprosy". A great variation was observed in the interpretation of the histopathological examination. The three pathologists reported "indeterminate leprosy" respectively in 7.0%, 54.4% and 84.2%, of the cases studied. A kappa index of agreement between any two pathologists ranged from 0.08 to 0.32, showing poor agreement between observers. Agreement improved by pooling together the reports "suggestive leprosy" and "indeterminate leprosy". The three pathologists agreed in the results of 24 biopsies of the 27 classified as leprosy by any one of the three observers. Eight cases were considered as "no leprosy" by all pathologists. Higher agreement indices were obtained for positive and negative proportionate concordance between any two examiners. The implications of the variation in the diagnosis of indeterminate leprosy and early leprosy are discussed in the context of public health and case-management.

Brazil↗

Surveillance of Trypanosoma cruzi transmission by serological screening of schoolchildren.

The seroprevalence of Trypanosoma cruzi infection among children is a sensitive indicator for assessing the effectiveness of programmes for control of Chagas disease. In this study we report the result of a cross-sectional serological survey carried out among schoolchildren living in a poor rural area in central Brazil. Eluates of blood collected on filter-paper were tested for anti-T. cruzi antibodies using immunofluorescence, haemagglutination, and enzyme-linked immunosorbent assays. The overall seroprevalence of T. cruzi infection was 7.9%, which compared with the findings of the national survey carried out in 1975-80 indicates that a twofold-to-threefold reduction in prevalence has occurred over the last 10 years. This is consistent with a reduction of transmission in the area, probably related to vector control efforts. Based on our results, the incidence of new cases was estimated to be 44 per annum in the study region. In rural areas with a scattered population, surveillance of T. cruzi transmission by serological screening of children at school entry is more practical and economical than entomological evaluation for assessing both the risk of transmission in the community and the efficacy of vector control measures. A sample size of around 1000 schoolchildren is sufficient to detect prevalences as low as 2%, and such an approach would be practical and applicable to most areas where Chagas disease is endemic.

Antibodies, Protozoan↗